Local circuit allowing hypothalamic control of hippocampal area CA2 activity and consequences for CA1

Elife. 2021 May 18:10:e63352. doi: 10.7554/eLife.63352.

Abstract

The hippocampus is critical for memory formation. The hypothalamic supramammillary nucleus (SuM) sends long-range projections to hippocampal area CA2. While the SuM-CA2 connection is critical for social memory, how this input acts on the local circuit is unknown. Using transgenic mice, we found that SuM axon stimulation elicited mixed excitatory and inhibitory responses in area CA2 pyramidal neurons (PNs). Parvalbumin-expressing basket cells were largely responsible for the feedforward inhibitory drive of SuM over area CA2. Inhibition recruited by the SuM input onto CA2 PNs increased the precision of action potential firing both in conditions of low and high cholinergic tone. Furthermore, SuM stimulation in area CA2 modulated CA1 activity, indicating that synchronized CA2 output drives a pulsed inhibition in area CA1. Hence, the network revealed here lays basis for understanding how SuM activity directly acts on the local hippocampal circuit to allow social memory encoding.

Keywords: area CA2; hippocampal circuitry; hippocampus; inhibition; mouse; neuroscience; social memory; supramammillary nucleus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • CA1 Region, Hippocampal / physiology*
  • CA2 Region, Hippocampal / physiology*
  • Cell Line
  • Hypothalamus / physiology*
  • Male
  • Memory
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Net / physiology*
  • Pyramidal Cells / physiology

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.